WT1 (Wilms tumor suppressor gene)
1999-10-01 Manfred Gessler AffiliationTheodor-Boveri-Institut fuer Biowissenschaften, Lehrstuhl Physiol. Chemie I, Am Hubland, D-97074 Wuerzburg, Germany
Identity
HGNC
LOCATION
11p13
LOCUSID
ALIAS
AWT1,GUD,NPHS4,WAGR,WIT-2,WT33
FUSION GENES
DNA/RNA
Description
10 exons spanning 48 kb of genomic DNA
Transcription
3 kb mRNA; four alternative splice forms: +/- exon 5 and alternative splice donor sites at exon 9
Proteins
Description
four major isoforms (429-449 aa) due to alternative splicing; there are eight minor isoforms resulting from different initiation sites (upstream CTG: 502-522 aa, downstream ATG: 303-323 aa)
Expression
kidney, spleen, mesothelia
Localisation
nuclear staining, either diffuse or in speckles, depending on isoform and mutations
Function
zinc finger transcription factor (4 C2H2-type fingers)
Homology
Sp1, Egr-1
Mutations
Germinal
various types of mutations, mostly affecting zinc fingers in exons 7-10. (WAGR syndrome, genito-urinary (GU) anomalies, Denys-Drash-syndrome, Frasier syndrome; see below)
Somatic
biallelic inactivation in Wilms tumors (
Implicated in
Entity name
Wilms tumor
Disease
nephroblastoma of childhood
Prognosis
good with treatment according to NWTS or SIOP
Cytogenetics
11p13 deletions/translocations can be seen in some cases
Oncogenesis
up to 15% of tumors show mainly biallelic inactivation of WT1 through deletion or mutatio
Entity name
Prognosis
poor
Cytogenetics
translocations, t(11;22)(p13;q12)
Fusion protein
With EWS: EWS-WT; in frame fusion of EWS exons 1-7 and WT1 exons 8-10
Entity name
Denys-Drash syndrome (DDS)
Disease
defined by: mesangial sclerosis with kidney failure (age 2 yrs), gonadal dysgenesis, risk of Wilms tumors
Prognosis
kidney failure at age 0-5 years
Hybrid gene
dominant negative mutations, especially missense mutations within the zinc fingers (aa 394 Arg -> Trp) but very few nonsense mutations
Oncogenesis
high risk of Wilms tumor development
Entity name
Disease
defined by: complete gonadal dysgenesis, focal glomerular sclerosis, gonadoblastoma; in karyotypic females the syndrome may be limited to focal glomerular sclerosis with regular gonadal development and function
Prognosis
kidney failure at age 10-30 years
Hybrid gene
heterozygous point mutations of alternative splice donor site in exon 9 with imbalance of WT1 isoform ratio
Oncogenesis
gonadoblatoma may occur within streak gonads
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 8382938 | 1993 | The expression of the Wilms' tumour gene, WT1, in the developing mammalian embryo. | Armstrong JF et al |
| 9398852 | 1997 | Donor splice-site mutations in WT1 are responsible for Frasier syndrome. | Barbaux S et al |
| 8621495 | 1996 | A non-AUG translational initiation event generates novel WT1 isoforms. | Bruening W et al |
| 2154335 | 1990 | Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. | Call KM et al |
| 7862627 | 1995 | Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor. | Gerald WL et al |
| 8019557 | 1994 | Infrequent mutation of the WT1 gene in 77 Wilms' Tumors. | Gessler M et al |
| 2154702 | 1990 | Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. | Gessler M et al |
| 1658787 | 1991 | Alternative splicing and genomic structure of the Wilms tumor gene WT1. | Haber DA et al |
| 9499425 | 1998 | Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms. | Klamt B et al |
| 7736591 | 1995 | Subnuclear localization of WT1 in splicing or transcription factor domains is regulated by alternative splicing. | Larsson SH et al |
| 9090524 | 1997 | A clinical overview of WT1 gene mutations. | Little M et al |
| 1655284 | 1991 | Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. | Pelletier J et al |
| 2244209 | 1990 | Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence. | Rauscher FJ 3rd et al |
| 10438524 | 1999 | Internal translation initiation generates novel WT1 protein isoforms with distinct biological properties. | Scharnhorst V et al |
| 8170946 | 1994 | Fine structure analysis of the WT1 gene in sporadic Wilms tumors. | Varanasi R et al |
Other Information
Locus ID:
NCBI: 7490
MIM: 607102
HGNC: 12796
Ensembl: ENSG00000184937
Variants:
dbSNP: 7490
ClinVar: 7490
TCGA: ENSG00000184937
COSMIC: WT1
RNA/Proteins
Expression (GTEx)
Pathways
| Pathway | Source | External ID |
|---|---|---|
| Transcriptional misregulation in cancer | KEGG | ko05202 |
| Transcriptional misregulation in cancer | KEGG | hsa05202 |
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA445084 | Wilms Tumor | Disease | DataAnnotation, Literature, MultilinkAnnotation | associated | 23788249 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38158126 | 2024 | EWSR1::WT1 Fusions in Neoplasms Other Than Conventional Desmoplastic Small Round Cell Tumor: Three Tumors Occurring Outside the Female Genital Tract. | 0 |
| 38219185 | 2024 | Familial focal segmental glomerulosclerosis associated with a WT1 gene missense mutation: A case report. | 0 |
| 38300383 | 2024 | WT1 and TP53 as valuable diagnostic biomarkers for relapse after hematopoietic stem cell transplantation in acute myeloid leukemia. | 0 |
| 38383842 | 2024 | MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFβ2-Smad2/3 signaling pathway in cervical cancer. | 0 |
| 38423183 | 2024 | Inhibition of transcriptional coactivator YAP Impairs the expression and function of transcription factor WT1 in diabetic podocyte injury. | 0 |
| 38588409 | 2024 | Comprehensive Transcriptomic Analysis of EWSR1::WT1 Targets Identifies CDK4/6 Inhibitors as an Effective Therapy for Desmoplastic Small Round Cell Tumors. | 0 |
| 38642153 | 2024 | Overexpression of WT1 in all molecular subtypes of breast cancer and its impact on survival: exploring oncogenic and tumor suppressor roles of distinct WT1 isoforms. | 0 |
| 38745948 | 2024 | Homeobox regulator Wilms Tumour 1 is displaced by androgen receptor at cis-regulatory elements in the endometrium of PCOS patients. | 0 |
| 38158126 | 2024 | EWSR1::WT1 Fusions in Neoplasms Other Than Conventional Desmoplastic Small Round Cell Tumor: Three Tumors Occurring Outside the Female Genital Tract. | 0 |
| 38219185 | 2024 | Familial focal segmental glomerulosclerosis associated with a WT1 gene missense mutation: A case report. | 0 |
| 38300383 | 2024 | WT1 and TP53 as valuable diagnostic biomarkers for relapse after hematopoietic stem cell transplantation in acute myeloid leukemia. | 0 |
| 38383842 | 2024 | MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFβ2-Smad2/3 signaling pathway in cervical cancer. | 0 |
| 38423183 | 2024 | Inhibition of transcriptional coactivator YAP Impairs the expression and function of transcription factor WT1 in diabetic podocyte injury. | 0 |
| 38588409 | 2024 | Comprehensive Transcriptomic Analysis of EWSR1::WT1 Targets Identifies CDK4/6 Inhibitors as an Effective Therapy for Desmoplastic Small Round Cell Tumors. | 0 |
| 38642153 | 2024 | Overexpression of WT1 in all molecular subtypes of breast cancer and its impact on survival: exploring oncogenic and tumor suppressor roles of distinct WT1 isoforms. | 0 |
Citation
Manfred Gessler
WT1 (Wilms tumor suppressor gene)
Atlas Genet Cytogenet Oncol Haematol. 1999-10-01
Online version: http://atlasgeneticsoncology.org/gene/78/wt1-(wilms-tumor-suppressor-gene)
